The journey from DNA to phenotype

Question 1 - How are traits inherited?

Gregor Mendel - initiated studies that would open up Darwin’s “black box”

-Presented work on heredity in 1865

-Attempted to demonstrate the usefulness of laws of heredity for evolution, was ignored

Mendel and the Garden Pea

• Gregor Mendel performed experiments with garden peas– peas are ideally suited to the study of

heredity• many varieties are available with easily

distinguishable traits that can be quantified• they are small, easy to grow, and produce large

numbers of offspring quickly• their reproductive organs can be easily

manipulated so that pollination can be controlled• they can self-fertilize

Mendel’s basic experimental design

Mendel’s first experiment on Heredity

- Do Peas “Breed True”

Yes. Traits are inherited from parents to offspring

- Why was this necessary?

Mendel’s second experiment:

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

-Bread varieties with different traits

-Carried out breeding for multiple generations (F1, F2…)

-Found that one trait was lost during F1 generation, but returned in lower numbers in F2 generation 3:1 (75%:25%)

-Concluded that each trait has 2 “factors”

-Concluded that each “factor” segregates independently during formation of sex cells (1st law of heredity)

Mendel’s third experiment:

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

-Bread varieties with multiple alternative traits

-Observed 9:3:3:1 ratio, including new combinations of traits

-Concluded that traits are independently assorted. 2nd law of heredity.

-(This law isn’t always correct, and probably shouldn’t be called a law)

Mendel’s conclusions

• Hypothesis 1– parents do not transmit traits directly to their offspring– parents transmit information about the trait in the form of

what Mendel called factors• in modern terms, Mendel’s factors are called genes

• Hypothesis 2– each parent contains two copies of the factor governing

each trait– the two copies of the factor may or may not be the same

• homozygous individuals have two of the same copies• heterozygous individuals have two different copies

Mendel’s conclusions

• Hypothesis 3– alternative forms of a factor lead to alternative traits– alleles are defined as alternative forms of a factor– appearance is determined by the alleles an individual

receives from its parents• the alleles present are the individual’s genotype• the expression of the alleles is the appearance or phenotype

Mendel in current knowledge

• We now know that genes are carried on chromosomes, with different alleles on the different homologues.

• The location of a gene on a chromosome is called its locus.

Figure 11.6 Alternative alleles of genes are located on homologous chromosomes

Mendel’s Laws

– Mendel’s First Law: Segregation• the two alleles of a trait separate from each

other during the formation of gametes, so that half of the gametes will carry one allele and half the gametes will carry the other allele

Mendel’s laws

– Mendel’s Second Law: Independent Assortment

• genes located on different chromosomes are inherited independently of one another

Not all traits show “Mendelian inheritance”

• Often the expression of phenotype is not straightforward

• Continuous variation– characters can show a range of small

differences when multiple genes act jointly to influence a character

• this type of inheritance is called polygenic

Height is a continuously varying character

Why Some Traits Don’t Show Mendelian Inheritance

• Environmental effects– the degree to which many alleles are

expressed depends on the environment– for example, some alleles are heat-

sensitive• arctic foxes only produce fur pigment when

temperatures are warm

Environmental effects on an allele

Mendel was ignored because the mechanism of heredity was unknown

-Darwin’s black box was Mendel’s black box too

-Mendel’s results were replicated by 3 others in 1900, geneticists started taking Mendel seriously

-Question 2 - Where are the genes within a cell?

-Walter Sutton published “The chromosomes in heredity” in 1903

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

“Gene Linkage” occurs when two genes reside on the same chromosome - violates the 2nd law of heredity

- Gene linkage can be broken by “crossing over” during meiosis

Chromosome mapping

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

-Morgan and undergrads looked at “mutations” in fruit flies

-Could use the frequency of “recombinants” (broken linkage groups) to estimate the relative positions of genes on a chromosome

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

Breaking gene Linkage

-Morgan et al. helped establish that genes reside on chromosomes.

Could map the relative distance of genes on a chromosome

Could explain all of Mendel’s results with genetics (Morgan) and cytology (Sutton)

-Morgan was not taken seriously by classic biologists. Where do mutations come from?

Are “fruit fly” mutations significant enough for large scale evolution?

By the mid 1900’s biologist could say

-Genes segregate independently in sex cells

-Genes reside on chromosomes

-Give a relative position to genes on chromosomes

-Could explain much of Darwin’s black box by genes on chrom., inherited by offspring with crossing over, mutation

Question 3 - What are genes?

- DNA or Protein? (Chromosomes are made of both)

- Genes must be able to self replicate to allow heredity

Various observations suggested that genes are correlated to with enzymes……..

……..Do genes control enzymes, are enzymes synthesized by genes?

Heat killed bacteria particles can “transform” living bacteria

(1944) Avery, MacLeod, McCarthy - Transforming particle is DNA:

-Purified DNA from extract could transform, purified protien could not

-Treatment of DNA with DNAse inhibits transformation, protinase does not

Question 4: How does DNA encode genetic information?

What is the structure of DNA?

X-Ray diffraction photograph

Discovering the Structure of DNA

• Rosalind Franklin’s work in 1953 using X-ray diffraction revealed that DNA had a regular structure that was shaped like a corkscrew, or helix

• Francis Crick and James Watson elaborated on the discoveries of Franklin and Chargaff and deduced that the structure of DNA was a double helix– two strands of DNA bound together by hydrogen bonds

between the bases

The DNA double helix

DNA is a double stranded helical molecule

-Strands held together by hydrogen bonds

-Bases pair with specific partners adinine:thymine, guanine:cytosine

-There are the same number of Gs and Cs, As and Ts

-Base pairing had been previously predicted from nucleotide ratios

Double stranded molecule also suggested that each strand could serve as a template during replication

Hypothetical models for DNA synthesis:

Favored model

How the DNA Molecule Copies Itself

• Matthew Meselson and Franklin Stahl tested, in 1958, the three alternative hypotheses for the replication of DNA – they used radioactive isotopes of N to label

DNA at different stages of replication– they found that DNA replication was semi-

conservative

What are the predictions from each hypothesis?

Strands of DNA are directional

Building the leading and lagging strands

The Role of Mutations in Human Heredity

• Accidental changes in genes are called mutations– mutations occur only rarely and almost always

result in recessive alleles• not eliminated from the population because they

are not usually expressed in most individuals (heterozygotes)

• in some cases, particular mutant alleles have become more common in human populations and produce harmful effects called genetic disorders

2 mechanisms of Mutation

• There are two general ways in which the genetic message encoded in DNA can be altered– mutation

• results from errors in replication• can involve changes, additions, or deletions to nucleotides

– recombination• causes change in the position of all or part of a gene

Mutation

• Mutations can alter the genetic message and affect protein synthesis– because most mutations occur randomly in a cell’s DNA,

most mutations are detrimental– the effect of a mutation depends on the identity of the cell

where it occurs• mutations in germ-line cells

– these mutations will be passed to future generations– they are important for evolutionary change

• mutations in somatic cells– not passed to future generations but passed to all other somatic

cells derived from it

Base substitution mutation

Mutation are the ultimate source of variation for evolution

• All evolutionary change begins with alterations in the genetic message– mutation and recombination provide the

raw materials for evolution

The journey from DNA to phenotype